Depression is one of the most common mental diseases. The incidence of this disease is about 5% of the world's population and it seriously affects our health and daily life. It is predicted that by 2020, depression will become the second most deadly illness that bothers our well-being and shortens our life span (second only to ischemic heart diseases.)
Although many antidepressants have been used clinically, many patients still suffer from depression after treatment because of the poor efficacy and latent side effects of some drugs. For many patients, electricity convulsion treatment remains necessary. Therefore, the development of antidepressants is definitely among the top popular topics in new medicine research. Many pharmaceutical companies invest massive funds into developing better antidepressants. The pathogenesis of depression is unknown, but is thought to be related to transmission impediment of 5-Hydroxytrypta mine (5-HT) and noradrenalin (NA) at synapses in the brain. Taking this point into consideration, the research of antidepressants usually focuses on enhancing the transmission function of NA and 5-HT at synapses in the brain. Due to many side effects of traditional TCA antidepressants, it will eventually be replaced by selective serotonin-reuptake inhibitors (SSRI) and other new generations of antidepressants. In the past 20 years, the appearance of SSRI, represented by fluoxetine, made a big progress in the treatment of depression. The main advantages of this kind of antidepressants are fewer side effects, convenient administration, -- and better tolerance; therefore, it is usually chosen as the first-line treatment to most patients suffering from depression. Reboxetine, which was marketed for the first time in 1997 in the United Kingdom, is the first drug of selective Norepinephrine-reuptake Inhibitors (NARI). This drug has better tolerance and better effects than SSRI in the treatment of depression. Another kind of new medicine is NA and specific 5-HT antidepressants such as Mirtazapine and Mianserine. These medicines involve both serotonergic and noradrenergic enhancement through blockade of the α2-autoreceptor and α2-heteroreceptor, increasing the release of NA and 5-HT in the synapses. American Home Products, Inc. (AHP) released a new antidepressant drug under the tradename Venlafaxine in 1997, which is the first one that is capable of inhibiting both NA and 5-HT reuptake (SNRI). Its characteristic is its rapid pharmacodynamic response. This is significant because slow response is seen as concern in other modern antidepressants. Venlafaxine has shown to be effective at treating severe and chronical depression. Compared with SSRI, the understanding of the SNRI compounds is limited.
Although different types of antidepressants have their own merits, it seems that there is no such drug that is particularly effective. Improvement is only made on their tolerance; and most of them have strong inhibitory actions to the cytochrome P450 system. Therefore, the antidepressants on the market today still cannot satisfy the need of treating depression. Many companies are studying different 5-HT subtype acceptor inhibitors. In addition, the launch of dual-acting antidepressants have prompted efforts to develop new antidepressants having triple actions on 5-HT, NA and DA systems.